Conference play began on October 3, 2015 with a 44–24 win against West Virginia in Norman, Oklahoma and ended with a 58–23 win against Oklahoma State in Stillwater, Oklahoma on November 28, 2015. Oklahoma finished conference play with an 8–1 record winning their ninth Big 12 Championship, their first since 2012.

Oklahoma was selected as the 4th seed to play in the 2015 College Football playoff against 1st seed Clemson on December 31, 2015 in the Orange Bowl which they lost 17–37. Oklahoma finished the season with an 11–2 record.

The Sooners hosted two non conference games against Akron and Tulsa and traveled to its other non conference foe Tennessee in Knoxville, Tennessee. Oklahoma met for the first time against the Akron Zips at home to open the season. The Sooners then traveled to Tennessee after defeating the Tennessee Volunteers last season and then hosted in-state rival Tulsa after traveling to Tulsa last year.